This application forms a portion of proposed research by a consortium known as the Cooperative Cataract Research Group (CCRG) which has been organized to encourage research concerning the human lens and causes of cataract formation. A portion of the effort of the present application will be devoted towards collection, processing, morphological classification and sharing with other centers of surgically-removed cataracts and clear lenses from Eye Bank eyes. Additionally, certain data derived from such lenses and useful research techniques concerning problems in common are expected to be shared between consortium research centers. Research at this center will utilize cataracts and clear human lenses concerning a variety of metabolic aspects concerning sulfur-containing amino acids and peptides. Establishment and detailed investigation of the enzymes which make up the biosynthetic pathway of cysteine, which uses methionine as the sulfur source (cystathionine pathway) will be initiated in the human lens. Other parameters concerning this enzyme pathway to be investigated in the human lens include: the effect of age, polyalcohols and morphological cataract type (as classified by the CCRG center in Boston) on the activity of selected enzymes of this pathway. The possible effect of cataract type upon residual enzyme activity will also be investigated using the glutathione synthetic system (Gamma-glutamylcysteine synthetase and glutathione synthetase) and glutathione peroxidase. The effect of age on glutathione peroxidase derived from clear human lenses will also be examined. These studies will further expand our knowledge of glutathione metabolism in the human lens, particularly the systems which aid in its synthesis, and one system which utilizes it in a protective mechanism. As a result, these investigations might aid in understanding certain specific mechanisms of cataract formation. The additional cooperation between a number of research centers is a further major benefit of this proposal.
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